Dataset Information

Beneficial effects of low alcohol exposure, but adverse effects of high alcohol intake on glymphatic function.

ABSTRACT: Prolonged intake of excessive amounts of ethanol is known to have adverse effects on the central nervous system (CNS). Here we investigated the effects of acute and chronic ethanol exposure and withdrawal from chronic ethanol exposure on glymphatic function, which is a brain-wide metabolite clearance system connected to the peripheral lymphatic system. Acute and chronic exposure to 1.5?g/kg (binge level) ethanol dramatically suppressed glymphatic function in awake mice. Chronic exposure to 1.5?g/kg ethanol increased GFAP expression and induced mislocation of the astrocyte-specific water channel aquaporin 4 (AQP4), but decreased the levels of several cytokines. Surprisingly, glymphatic function increased in mice treated with 0.5?g/kg (low dose) ethanol following acute exposure, as well as after one month of chronic exposure. Low doses of chronic ethanol intake were associated with a significant decrease in GFAP expression, with little change in the cytokine profile compared with the saline group. These observations suggest that ethanol has a J-shaped effect on the glymphatic system whereby low doses of ethanol increase glymphatic function. Conversely, chronic 1.5?g/kg ethanol intake induced reactive gliosis and perturbed glymphatic function, which possibly may contribute to the higher risk of dementia observed in heavy drinkers.

SUBMITTER: Lundgaard I

PROVIDER: S-EPMC5797082 | biostudies-other | 2018 Feb

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Beneficial effects of low alcohol exposure, but adverse effects of high alcohol intake on glymphatic function.

Lundgaard Iben I Wang Wei W Eberhardt Allison A Vinitsky Hanna Sophia HS Reeves Benjamin Cameron BC Peng Sisi S Lou Nanhong N Hussain Rashad R Nedergaard Maiken M

Scientific reports 20180202 1

Prolonged intake of excessive amounts of ethanol is known to have adverse effects on the central nervous system (CNS). Here we investigated the effects of acute and chronic ethanol exposure and withdrawal from chronic ethanol exposure on glymphatic function, which is a brain-wide metabolite clearance system connected to the peripheral lymphatic system. Acute and chronic exposure to 1.5 g/kg (binge level) ethanol dramatically suppressed glymphatic function in awake mice. Chronic exposure to 1.5 g ...[more]

PMID: 29396480

Similar Datasets

Project description:Background and aimsBoth high alcohol intake and alcohol dependence increase mortality, and both are associated with smoking. We aimed to compare the associations of quantity of alcohol, number of alcohol-related symptoms and smoking history with all-cause mortality, and to assess symptom count and smoking history as confounders or mediators of the effects of high alcohol intake.DesignSurvival was analysed by Cox regression with sex, body mass index, alcohol intake (overall and by beverage), maximum drinks on any day, alcohol symptom count and smoking status as potential predictors of age at death.SettingAustralia.ParticipantsParticipants were apparently healthy volunteers consisting of 33 593 Australian adult twins and their relatives who completed questionnaires or interviews between 1979 and 2005.MeasurementsData on alcohol use, smoking and occurrence of symptoms related to alcohol use disorders and death records from the Australian National Death Index.FindingsA total of 3764 participants were matched with deaths occurring within Australia up to July 2014. Individually, alcohol intake [hazard ratio (HR) = 1.0082, 95% confidence interval (CI) = 1.0063-1.0102, per drink per week], beer intake (HR = 1.0159, 95% CI = 1.0123-1.0195, per drink per week), life-time maximum number of drinks in 1 day (HR = 1.0176, 95% CI = 1.0130-1.0221, per drink), symptom count (HR = 1.0867, 95% CI = 1.0633-1.1106, per symptom) and smoking status (HR = 2.82, 95% CI = 2.52-3.16 for smokers of 10+ cigarettes/day versus never-smokers) were each significant predictors of all-cause mortality. After adjustment for the independently significant predictors alcohol symptom count and smoking status, alcohol intake was no longer significant (adjusted HR = 1.0012 per drink per week, 95% CI = 0.9979-1.0145).ConclusionsNumber of symptoms related to high alcohol intake and tobacco smoking appear to account for the positive association between alcohol consumption and premature mortality.

Project description:Intake of high-protein (HP) diets has increased over the last years, mainly due to their popularity for body weight control. Liver is the main organ handling ingested macronutrients and it is associated with the beginning of different pathologies. We aimed to deepen our knowledge on molecular pathways affected by long-term intake of an HP diet. We performed a transcriptome analysis on liver of rats chronically fed with a casein-rich HP diet and analyzed molecular parameters related to liver injury. Chronic increase in the dietary protein/carbohydrate ratio up-regulated processes related with amino acid uptake/metabolism and lipid synthesis, promoting a molecular environment indicative of hepatic triacylglycerol (TG) deposition. Moreover, changes in expression of genes involved in acidâbase maintenance and oxidative stress indicate alterations in the pH balance due to the high acid load of the diet, which has been linked to liver/health damage. Up-regulation of immune-related genes was also observed. In concordance with changes at gene expression level, we observed increased liver TG content and increased serum markers of hepatic injury/inflammation (aspartate transaminase, C-reactive protein and TNF-alpha). Moreover, the HP diet strongly increased hepatic mRNA and protein levels of HSP90, a marker of liver injury. Thus, we show for the first time that long-term consumption of an HP diet, resulting in a high acid load, results in a hepatic transcriptome signature reflecting increased TG deposition and increased signs of health risk (increased inflammation, alterations in the acidâbase equilibrium and oxidative stress). Persistence of this altered metabolic status could have unhealthy consequences. Wistar wildtype male rats, aged 8 weeks, received a low fat diet, high protein or high fat diet for 4 months. After sacrification, livers were dissected, and immediately snap frozen in liquid nitrogen. Total RNA was isolated, quantified and qualified, and subsequently used for global gene expression profiling using Agilent 4x44K microarrays.

Dataset Information

Beneficial effects of low alcohol exposure, but adverse effects of high alcohol intake on glymphatic function.

Publications

Beneficial effects of low alcohol exposure, but adverse effects of high alcohol intake on glymphatic function.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets